Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival.
BACKGROUND
Acute myelogenous leukemia (AML) associated with core-binding-factor (CBF) abnormalities is the type of leukemia most responsive to cytarabine (ara-C) therapy and is of relative favorable prognosis. In vitro and ex vivo observations suggest that increases in intracellular ara-C levels influenced by administration of fludarabine and granulocyte colony-stimulating factor (GCSF) increase the effect of ara-C, prompting us to clinically evaluate the efficacy of such combinations.


METHODS
We analyzed the event-free survival of patients with newly diagnosed CBF AML treated with fludarabine and ara-C (FA) (N = 45) or with FA and GCSF (FLAG) (N = 22) and compared results to patients treated with regimens consisting of idarubicin and ara-C with or without GCSF (IA/IAG) (N = 47).


RESULTS
After accounting for prognostic covariates other than treatment (including year in which treatment was administered), FA, and in particular FLAG, were associated with longer event-free survival than IA/IAG.


CONCLUSIONS
Thus, our data lends clinical credence to the observed modulation of ara-C by fludarabine and GCSF.
Borthakur
Gautam
G
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. gborthak@mdanderson.org
Kantarjian
Hagop
H
Wang
Xuemei
X
Plunkett
William K
WK
Gandhi
Varsha V
VV
Faderl
Stefan
S
Garcia-Manero
Guillermo
G
Ravandi
Farhad
F
Pierce
Sherry
S
Estey
Elihu H
EH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D050660:Core Binding Factors / Q000378:metabolism*; D003561:Cytarabine / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D050660:Core Binding Factors; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine; D015255:Idarubicin